Current Therapeutic Research-clinical and Experimental最新文献

{"title":"Evaluation of Rosuvastatin Therapy on SIRT1 Gene Expression in Patients with Multiple Sclerosis: An Uncontrolled Clinical Trial","authors":"Shakiba Batoee Pharm.D ,&nbsp;Maryam Etminaniesfahani Pham.D, Ph.D ,&nbsp;Mehrdokht Mazdeh MD, Specialist in neurological diseases ,&nbsp;Alireza Soltanian Ph.D ,&nbsp;Fatemeh Nouri PharmD, PhD","doi":"10.1016/j.curtheres.2023.100718","DOIUrl":"https://doi.org/10.1016/j.curtheres.2023.100718","url":null,"abstract":"<div><h3>Background</h3><p>Multiple sclerosis (MS) is a chronic autoimmune disease. Current medications have some limitations such as low efficacy and high side effects. In recent years, statins have been raised as potential therapeutics for MS treatment with minimal complications. In addition, patient monitoring using suitable molecular markers is necessary for treatment response evaluation.</p></div><div><h3>Objective</h3><p>The aim of the present study was the evaluation of <em>SIRT1</em> gene expression changes following rosuvastatin therapy in patients with MS.</p></div><div><h3>Methods</h3><p>This before–after uncontrolled clinical trial study was performed on 25 patients with MS. Patients were treated with 20 mg rosuvastatin daily for 3 months. The Expanded Disability Status Scale (EDSS) was measured before and after statin therapy. Blood samples were taken from patients 2 times, before and after statin therapy, and centrifuged for white blood cell isolation. Total RNA was extracted using RNX-plus reagent, and complementary DNA was synthesized using Pars Tous cDNA Synthesis Kit. Real-time polymerase chain reaction was done using SYBR blue master mix and gene-specific primers in Roche light cycler. Patients’ information was recorded using a checklist. Data analysis was performed using SPSS version 23 and Graph Pad version 9 software and <em>P</em> &lt; 0.05 was considered a significant level.</p></div><div><h3>Results</h3><p><em>SIRT1</em> was significantly upregulated in MS patients after statin therapy. Subsequently, EDSS of patients was decreased along with the increase in <em>SIRT1</em> gene expression, although EDSS changes were not significant (<em>P</em> &gt; 0.05). Pearson correlation test showed no significant relationship between EDSS and <em>SIRT1</em> gene expression (<em>P</em> &gt; 0.05). No significant relationship was observed between <em>SIRT1</em> expression or EDSS levels with patients’ age, sex, weight, height, and body mass index and administrated drugs (<em>P</em> &gt; 0.05).</p></div><div><h3>Conclusions</h3><p><em>SIRT1</em> potentially is a sensitive and reliable biomarker for patients with MS monitoring during statin therapy.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"99 ","pages":"Article 100718"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X23000279/pdfft?md5=71c227af18d89c05bd8f555795416d6f&pid=1-s2.0-S0011393X23000279-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92132758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three Weekly Intra-Articular Injections of Hylan G-F 20 vs Arthrocentesis in Patients with Chronic Idiopathic Knee Osteoarthritis: A Multicenter, Evaluator- and Patient-Blinded, Randomized Controlled Trial","authors":"Yili Huang DO ,&nbsp;Peter Lascarides DO ,&nbsp;Wilson Ngai PharmD, MSc, MBA ,&nbsp;Kevin Steele PharmD, MHA ,&nbsp;Charles D. Hummer MD","doi":"10.1016/j.curtheres.2023.100707","DOIUrl":"10.1016/j.curtheres.2023.100707","url":null,"abstract":"<div><h3>Background</h3><p>Knee osteoarthritis is a leading cause of disability worldwide. Symptoms can vary over time, leading to episodes of worsened symptoms known as flares. Intra-articular injection of hyaluronic acid has demonstrated long-term symptomatic relief in the broader knee osteoarthritis population, although its use in the flare population has not been extensively examined.</p></div><div><h3>Objective</h3><p>To assess the efficacy and safety of 3 once-weekly intra-articular injections of hylan G-F 20 (as single and repeat courses) in patients with chronic knee osteoarthritis, including a subpopulation that experienced flare.</p></div><div><h3>Methods</h3><p>Prospective randomized controlled, evaluator- and patient-blinded, multicenter trial with 2 phases: hylan G-F 20 vs arthrocentesis only (control) and 2 courses vs single-course hylan G-F 20. Primary outcomes were visual analog scale (0–100 mm) pain scores. Secondary outcomes included safety and synovial fluid analysis.</p></div><div><h3>Results</h3><p>Ninety-four patients (104 knees) were enrolled in Phase I, with 31 knees representing flare patients. Seventy-six patients (82 knees) were enrolled in Phase II. Long-term follow-up was 26 to 34 weeks. In flare patients, hylan G-F 20 showed significantly more improvement than the controls for all primary outcomes except pain at night (<em>P</em> = 0.063). Both 1 and 2 courses of hylan G-F 20 showed significant improvements from baseline for primary outcomes with no differences in efficacy between groups in the intention-to-treat population at the end of Phase II. Two courses of hylan G-F 20 showed better improvement in pain with motion (<em>P</em> = 0.0471) at long-term follow-up. No general side effects were reported, and local reactions (pain/swelling of the injected joint) resolved within 1 to 2 weeks. Hylan G-F 20 was also associated with reduced effusion volume and protein concentration.</p></div><div><h3>Conclusions</h3><p>Hylan G-F 20 significantly improves pain scores vs arthrocentesis in flare patients with no safety concerns. A repeat course of hylan G-F 20 was found to be well tolerated and efficacious.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"99 ","pages":"Article 100707"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0f/80/main.PMC10319210.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9807301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Care Resource Use Among Patients with Advanced Non–Small Cell Lung Cancer in Japan, 2017–2019","authors":"Yasushi Goto MD, PhD ,&nbsp;Kodai Kawamura MD, PhD ,&nbsp;Tatsuro Fukuhara MD, PhD ,&nbsp;Yukiko Namba MD, PhD ,&nbsp;Keisuke Aoe MD, PhD ,&nbsp;Takehito Shukuya MD, PhD ,&nbsp;Takeshi Tsuda MD ,&nbsp;Melissa L. Santorelli PhD, MPH ,&nbsp;Kazuko Taniguchi MS ,&nbsp;Tetsu Kamitani MD, PhD ,&nbsp;Masato Irisawa PhD ,&nbsp;Kingo Kanda MPharm ,&nbsp;Machiko Abe MS ,&nbsp;Thomas Burke PharmD, PhD ,&nbsp;Hiroshi Nokihara MD, PhD","doi":"10.1016/j.curtheres.2023.100712","DOIUrl":"10.1016/j.curtheres.2023.100712","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;First-line immune checkpoint inhibitor (ICI) monotherapy for advanced non–small cell lung cancer (NSCLC) was introduced in Japan in February 2017. Limited information is available since that time regarding health care resource use for NSCLC in Japan, where the hospitalization burden is high.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;p&gt;We evaluated health care resource use from first- through third-line systemic anticancer therapy for patients with advanced NSCLC included in a multicenter, retrospective chart review study.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Eligible patients were aged 20 years or older with unresectable locally advanced/metastatic NSCLC with no known actionable genomic alteration who initiated first-line systemic anticancer therapy from July 1, 2017, to December 20, 2018, at 23 Japanese hospitals. We calculated the percentage of patients with a record of each resource used, the total number of each resource, and the resource use per 100 patient-weeks of follow-up from initiation of first-, second-, and third-line therapy, overall and by the 3 most common regimen categories, namely, ICI monotherapy, platinum-doublet chemotherapy (without concomitant ICI), and nonplatinum cytotoxic regimens (nonplatinum). Study follow-up ended September 30, 2019.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Among 1208 patients (median age = 70 years; 975 [81%] men), 463 patients (38%) received ICI monotherapy, 647 (54%) received platinum-doublet chemotherapy, and 98 (8%) received nonplatinum regimens as first-line therapy. During the study, 621 (51%) patients initiated second-line, and 281 (23%) initiated third-line therapy. The majority of patients experienced ≥1 hospitalization (76%–94%) and ≥1 outpatient visit (85%–90%) during each therapy line. The number of hospitalizations increased from 6.5 per 100 patient-weeks in first-line to 8.0 per 100 patient-weeks in third-line. During first-line therapy, the number of hospitalizations per 100 patient-weeks were 4.8, 8.4, and 6.5 for patients receiving ICI monotherapy, platinum-doublet chemotherapy, and nonplatinum regimens, respectively, and the percentages of hospitalizations categorized as attributable to NSCLC treatment administration (no surgery, procedure, treatment of metastasis, or palliative lung radiation) were 64%, 77%, and 73%, respectively. The number of outpatient visits increased from 43.0 per 100 patient-weeks in first-line to 51.4 per 100 patient-weeks in third-line therapy. During first-line therapy, outpatient visits per 100 patient-weeks were 41.0, 46.7, and 33.0 for patients receiving ICI monotherapy, platinum-doublet chemotherapy, and nonplatinum regimens, respectively, and the percentages of outpatient visits for infusion therapy were 48%, 34%, and 36%, respectively.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;The results of this study, although solely descriptive, showed differing patterns of health care resource use during first-line therapy among the 3 common systemic anticancer ","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"99 ","pages":"Article 100712"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b6/8a/main.PMC10372154.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9899700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the Relationship Between Gastric-Acid Suppressants and the Risk of Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis","authors":"Karamali Kasiri Associate ,&nbsp;Catherine M.T. Sherwin Professor ,&nbsp;Sahar Rostamian MD ,&nbsp;Saeid Heidari-Soureshjani MSc","doi":"10.1016/j.curtheres.2023.100692","DOIUrl":"10.1016/j.curtheres.2023.100692","url":null,"abstract":"<div><h3>Background</h3><p>Esophageal cancer is a cancerous tumor that develops in the esophagus. It is the 10th most common cancer and has a low survival rate. Esophageal adenocarcinoma (EAC) is increasing in incidence globally. Those with EAC are affected by Barrett's esophagus metaplasia, which is attributed to genetic predisposition and is more common in men. Studies suggest that gastric acid suppressants, like proton pump inhibitors and histamine-2 receptor antagonists, have anticancer properties and reduce EAC. However, other research has suggested that they are not cancer-protective, and the use of antisecretory drugs is a risk factor for developing EAC.</p></div><div><h3>Objective</h3><p>This systematic review and meta-analysis investigated the properties and risk factors associated with using gastric acid suppressants in patients with EAC.</p></div><div><h3>Methods</h3><p>This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Information from selected articles, including the lead author's name, year of publication, study setting, sample size, and gender, was extracted and recorded into an Excel (Microsoft, Redmond, Washington) form. Statistical data included odds ratio, hazard ratio, and/or risk ratio, with a 95% CI associated with patients with EAC and receiving gastric acid suppressants. Data were compared with individuals not receiving treatment. Publication bias was assessed using Begg's and Egger's tests. Statistical analyzes used Stata 14.0 (Stata LLC, College Station, Texas).</p></div><div><h3>Results</h3><p>The initial electronic literature search retrieved 3761 titles/abstracts. Extensive screening selected 20 articles for analysis. Odds ratios associated with EAC in the individuals using gastric acid suppressants were 0.77 (95% CI, 0.49–1.22; <em>P</em> = 0.274) and 0.67 (95% CI, 0.39–1.29; <em>P</em> = 0.240) for proton pump inhibitors and 1.02 (95% CI, 0.44-2.36; <em>P</em> = 0.967) for histamine-2 receptor antagonists.</p></div><div><h3>Conclusions</h3><p>The results found that gastric acid suppressants do not have a protective role in EAC and are not risk factors. Future studies of confounding variables and risk factors are needed to understand what affects EAC development.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"98 ","pages":"Article 100692"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10748480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medical Cannabis Received by Patients According to Qualifying Condition in a US State Cannabis Program: Product Choice, Dosing, and Age-Related Trends","authors":"Xintian Lyu BS ,&nbsp;Sílvia M. Illamola PharmD, PhD ,&nbsp;Susan E. Marino PhD ,&nbsp;Ilo E. Leppik MD ,&nbsp;Stephen Dahmer MD ,&nbsp;Paloma Lehfeldt MD ,&nbsp;Jeannine M. Conway PharmD ,&nbsp;Rory P. Remmel PhD ,&nbsp;Kyle Kingsley MD ,&nbsp;Angela K. Birnbaum PhD","doi":"10.1016/j.curtheres.2023.100709","DOIUrl":"10.1016/j.curtheres.2023.100709","url":null,"abstract":"<div><h3>Background</h3><p>Little is known about the distribution of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to patients participating in state medical cannabis programs. The Minnesota cannabis program requires third-party testing of products with limited formulations of cannabis for distribution to patients.</p></div><div><h3>Objective</h3><p>To characterize the distribution of cannabis products, their CBD/THC content, and dosing among patients with qualifying conditions.</p></div><div><h3>Methods</h3><p>This is a retrospective analysis of ∼50% of registered users receiving medical cannabis in Minnesota (June 16, 2016, to November 15, 2019). Data included formulation, CBD/THC prescribed doses, and qualifying conditions. The primary end points were calculated using daily dose and duration of use. Comparisons were made for CBD and THC total daily dose dispensed, patient age, and approved product. Nonparametric statistical tests were used (significance was set at <em>p</em> &lt; 0.05).</p></div><div><h3>Results</h3><p>A total of 11,520 patients were listed with 1 qualifying condition. The most common condition was intractable pain (60.0%). Median dispensation duration varied from 53 days (cancer) to 322 days (muscle spasms). Most (≥62.8%) patients across all qualifying conditions received both CBD and THC. Median THC dose was lower in older (≥65 years) compared with younger adults with intractable pain (<em>p</em> &lt; 0.0001) and cancer patients (<em>p</em> = 0.0152), and the same pattern was found CBD dose with seizure (<em>p</em> = 0.0498) patients. For commercial products with Food and Drug Administration indications, the median CBD total daily dose was 86.9% lower than the recommended doses for patients with seizures (Epidiolex: Jazz Pharmaceuticals, Palo Alto CA) and median THC total daily dose was 65.3% (Syndros: Benuvia Manufacturing, Round Rock, TX) or 79.3% lower (Marinol: Banner Pharmacaps, Inc., High Point, NC) for cancer patients.</p></div><div><h3>Conclusions</h3><p>A majority of patients received products containing both CBD and THC. Dosages varied by age group and were lower than recommended for conditions with Food and Drug Administration-approved products. Complex pharmacokinetics of THC and CBD, possible age-related changes in physiology, unknown efficacy, and potential for drug interactions all increase the need for monitoring of patients receiving cannabis products. (<em>Curr Ther Res Clin Exp</em>. 2023; 84:XXX–XXX)</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"99 ","pages":"Article 100709"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/f7/main.PMC10393751.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9939709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence Studies of Sildenafil Citrate Orodispersible Film Administered with and without Water vs ViagraⓇ Film-Coated Tablets in Healthy Male Volunteers","authors":"Andrew Shaw PhD ,&nbsp;Tracey E. Lawrence PhD ,&nbsp;Tieliang Yan MSc ,&nbsp;Mark Liu MSc ,&nbsp;Nancy Summers RN, BSN ,&nbsp;Venkatesh Daggumati M. Pharm ,&nbsp;Sandy Tarr Austria ,&nbsp;Juan Carlos Rondon MD ,&nbsp;Sarah Hackley PhD ,&nbsp;Shivani Ohri Vignesh MD ,&nbsp;Tarek A. Hassan MD, MSc","doi":"10.1016/j.curtheres.2023.100708","DOIUrl":"https://doi.org/10.1016/j.curtheres.2023.100708","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Orodispersible film (ODF) formulation offers ease of use, convenience of administration, and other advantages, especially for patients who have difficulty in swallowing or are on liquid restriction compared with conventional oral formulations for the treatment of erectile dysfunction.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;p&gt;These studies compared the bioequivalence of 50 mg sildenafil citrate ODF formulation (test drug) with the marketed 50 mg sildenafil citrate film-coated tablet (FCT) (Viagra&lt;sup&gt;Ⓡ&lt;/sup&gt;; Pfizer, New York, NY) (reference drug), with and without water in 2 randomized cross-over studies.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Two randomized cross-over studies were conducted. The first study explored the bioequivalence of test drug administered with and without water compared with the reference drug with water. The second study investigated the bioequivalence of test drug, without water, compared with the reference drug with water. Forty-two and 80 healthy male volunteers were recruited in the first and second study, respectively. All volunteers fasted for 10 hours pre-dose. A 1-day washout period between doses was observed. Blood samples were collected at both before (up to 120 minutes before dosing) and after dosing (at different intervals up to 14 hours) stages. Statistical analyses on pharmacokinetic parameters were performed. Safety and tolerability for both the formulations were evaluated.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;In the first study, bioequivalence was demonstrated for sildenafil citrate ODF administered with water when compared with the Viagra&lt;sup&gt;Ⓡ&lt;/sup&gt; FCT. The ratios of adjusted geometric means (90% confidence interval (CI)) were maximum plasma concentration: 1.02 (94.91–108.78) and area under the plasma concentration-time curve: 1.09 (104.49–113.21) for sildenafil citrate ODF administered with water vs Viagra&lt;sup&gt;Ⓡ&lt;/sup&gt; FCT. These ratios were within the bioequivalence acceptance range of 80% to 125%, indicating that the bioequivalence criteria were met. The pharmacokinetic parameters for the second study also showed bioequivalence for sildenafil citrate ODF (without water) compared with Viagra&lt;sup&gt;Ⓡ&lt;/sup&gt; FCT. The ratios of adjusted geometric means (90% CI) were maximum plasma concentration: 1.02 (95.47–109.36) and area under the plasma concentration-time curve: 1.06 (103.42–108.40) for sildenafil citrate ODF administered without water vs Viagra&lt;sup&gt;Ⓡ&lt;/sup&gt; FCT. Adverse events in both the studies occurred at similar rates for the 2 formulations and were mild in intensity.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;These results suggest that the new ODF formulation can be used interchangeably with the marketed FCT formulation. Sildenafil citrate ODF administered with and without water met bioequivalence criteria compared with Viagra&lt;sup&gt;Ⓡ&lt;/sup&gt; FCT administered with water under fasted conditions in healthy adult male volunteers. The new ODF formulation can be used as a suitable alternative to the con","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"99 ","pages":"Article 100708"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49812940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory Effects of Modified Bovine Colostrum, Whey, and Their Combination with Other Natural Products: Effects on Human Peripheral Blood Mononuclear Cells","authors":"Xuesheng Han PhD, FACN ,&nbsp;David Vollmer PhD ,&nbsp;Elena Y. Enioutina MD, PhD","doi":"10.1016/j.curtheres.2023.100720","DOIUrl":"https://doi.org/10.1016/j.curtheres.2023.100720","url":null,"abstract":"<div><h3>Background</h3><p>Many natural products have immunomodulatory properties. However, the mechanism of immunomodulatory activities are poorly understood.</p></div><div><h3>Objectives</h3><p>This study evaluated the influence of bovine colostrum products, a whey product, or their combinations with other natural products on human peripheral blood mononuclear cells’ (PBMC) ability to produce cytokines upon activation.</p></div><div><h3>Methods</h3><p>PBMCs were pretreated with ultrafiltered colostrum, nano-filtered bovine colostrum, egg yolk extract, a botanical blend, colostrum + egg yolk extract, colostrum + egg yolk + botanical blend, and fermented whey and then stimulated with lipopolysaccharide or phytohemagglutinin. Cytokine production was measured by the Luminex assay.</p></div><div><h3>Results</h3><p>All study products demonstrated immunomodulatory properties by regulating cytokines production by activated PBMCs. Ultrafiltered colostrum alone displayed the highest immune stimulatory activity. It stimulated proinflammatory cytokine production by lipopolysaccharide-activated PBMCs and suppressed cytokine production by phytohemagglutinin-activated cells. Other study products mainly suppressed cytokine release by both cell types. The immunomodulatory properties depended upon the dose of the products used in the study.</p></div><div><h3>Conclusions</h3><p>All tested products modulated innate and adaptive immune cell activities. Most of the products demonstrated anti-inflammatory properties, except ultrafiltered colostrum, which stimulated the lipopolysaccharide-activated PBMC production of inflammatory cytokines. These products can be potentially used to support overall immune health.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"99 ","pages":"Article 100720"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49812944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Noncoding RNA Antisense Transcript of the B-Cell Translocation Gene 3 Regulation of BTG3 in Pancreatic Ductal Adenocarcinoma Tumor Progression","authors":"Jing Chen M.D. ,&nbsp;Ming-Yuan Zhu M.D. ,&nbsp;Yan-Hua Huang M.D. ,&nbsp;Yi-Ting Ling M.D. ,&nbsp;Tian-Yuan Gu M.D. ,&nbsp;Quan Zhou M.D. ,&nbsp;Ming-Jian Fei M.D. ,&nbsp;Zhong-Cheng Zhou M.D.","doi":"10.1016/j.curtheres.2023.100700","DOIUrl":"https://doi.org/10.1016/j.curtheres.2023.100700","url":null,"abstract":"<div><h3>Background</h3><p>Antisense transcript of the B-cell translocation gene 3 (ASBEL) is a highly conserved antisense non-coding RNA (ncRNA) and participates in a variety of biological processes. However, the ASBEL expression status in pancreatic ductal adenocarcinoma (PDAC) and its correlation with <em>BTG3</em> expression and tumor cell progression were not completely clear.</p></div><div><h3>Objective</h3><p>We conducted cell experiments and animal experiments to confirm that ASBEL plays a crucial role in the tumorigenesis of PDAC by targeting BTG3.</p></div><div><h3>Methods</h3><p>ASBEL regulation in PDAC tumorigenesis was evaluated using Western blotting, quantitative polymerase chain reaction, Cell Counting Kit-8 assay, flow cytometry, and cell transfection. We also evaluated the expression of ASBEL and <em>BTG3</em> in tumor tissues and cells using Western blotting and quantitative real-time polymerase chain reaction. Finally, we explored the role of ASBEL in tumor development by silencing or overexpressing <em>ASBEL</em> gene in AsPC-1 or CFPAC-1 cells, respectively, and evaluated the antitumor activity in vivo using an <em>ASBEL</em> antagonist.</p></div><div><h3>Results</h3><p>Our study revealed the expression of <em>ASBEL</em> in all pancreatic cell lines. The expression level of <em>ASBEL</em> in tumor tissues was found to be higher than that of paracarcinomatous tissues. ASBEL suppresses expression of <em>BTG3</em>, enhances proliferation and suppresses apoptosis, and promotes migration and invasion in pancreatic cancer cell. Antagonist regulates the expression of ASBEL in AsPC-1, and suppresses tumor growth in xenograft mouse model.</p></div><div><h3>Conclusions</h3><p>Our results indicate that <em>ASBEL</em> may play a tumor-promoting factor in PDAC by targeting <em>BTG3</em> and could be as an important biomarker for PDAC treatment. (<em>Curr Ther Res Clin Exp</em>. 2023; 84:XXX–XXX).</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"98 ","pages":"Article 100700"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49813289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Effect of Fixed Ratio Magnitude on the Rate of Lever-Pressing and Interinjection Intervals of Cocaine Self-Administration in Rats","authors":"Jhanvi N. Desai ,&nbsp;Abigail R. Muccilli ,&nbsp;Luis E. Tron Esqueda ,&nbsp;Jeffrey A. Welge PhD ,&nbsp;Andrew B. Norman PhD","doi":"10.1016/j.curtheres.2023.100727","DOIUrl":"10.1016/j.curtheres.2023.100727","url":null,"abstract":"<div><h3>Background</h3><p>Many features of self-administration behavior may be explained by reference to the properties of schedules of reinforcement. Schedules alter the probability of a behavior being reinforced and thereby increase, or decrease, the frequency of the behavior and fixed ratio (FR) magnitude reportedly alters the rate of responding to cocaine. A pharmacokinetic/pharmacodynamic interaction theory states that lever-pressing behavior is induced only when cocaine levels in the body are above the priming/remission threshold and below the satiety threshold—a range termed the compulsion zone. This theory successfully explains cocaine self-administration in rats on a progressive ratio and the FR1 schedule.</p></div><div><h3>Objectives</h3><p>To determine the effects of high FR magnitude on the rate of self-administration of cocaine and the rate of lever-pressing behavior when cocaine levels are within the compulsion zone.</p></div><div><h3>Methods</h3><p>Rats acquired cocaine self-administration on an FR1 schedule and then were switched to sessions that started with FR1 and then FR 5, 10, 20, or 50. An only FR1 session was run each week between FR1/FR50 sessions and then only FR1 sessions were conducted for several weeks.</p></div><div><h3>Results</h3><p>Interinjection intervals at a unit dose of 3 µmol/kg were regular at both FR1 and FR50 but were longer by the time required to complete the 50 presses. When responding by rats was maintained under an FR50 schedule of cocaine presentations, compared to baseline FR1 sessions, dramatic increases in the number of lever-presses were observed after access to cocaine was terminated, a previously unreported finding. However, lever-pressing occurred only when cocaine levels were in the compulsion zone, and this duration was unchanged. The increase in lever-pressing persisted for weeks. Interinjection intervals at FR1 were not altered after exposure to FR50.</p></div><div><h3>Conclusions</h3><p>Although previously considered key to understanding the regulation of cocaine self-administration behavior, FR magnitude simply increased interinjection intervals by the time required to complete 50 lever-presses. The dramatic increase in the rate of lever-pressing was caused by the high FR schedule rather than cocaine. The utility of the schedule-induced increase in the rate of lever-pressing is unclear. The compulsion zone theory provides a rational pharmacological basis for understanding cocaine self-administration behavior.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"99 ","pages":"Article 100727"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X2300036X/pdfft?md5=be8d20eb5e723e485f2f52cf3436426e&pid=1-s2.0-S0011393X2300036X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135455001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of Nasal Liposome Formulation of Venlafaxine Hydrochloride using a Box-Behnken Experimental Design","authors":"Sulekha Khute MPharm,&nbsp;Rajendra K. Jangde PhD, MPharm","doi":"10.1016/j.curtheres.2023.100714","DOIUrl":"10.1016/j.curtheres.2023.100714","url":null,"abstract":"<div><h3>Background</h3><p>Intranasal administration is among the most effective alternatives to deliver drugs directly to the brain and prevent first-pass metabolism. Venlafaxine-loaded liposomes are biocompatible carriers that enhance transport qualities over the nasal mucosa.</p></div><div><h3>Objective</h3><p>This research aimed to develop, formulate, characterize, and observe the prepared formulation.</p></div><div><h3>Methods</h3><p>The formulation was developed using the thin-film hydration technique. The response surface plot interrelationship between three independent variables are lipid, cholesterol and polymer and four dependent variables such as particle size, percentage entrapment efficiency, and percentage drug release were ascertained using the Box-Behnken design.</p></div><div><h3>Results</h3><p>The drug-release chitosan-coated liposomes were reported to have a particle size distribution, entanglement efficiency, and 84%, respectively, of 191 ± 34.71 nm, 94 ± 2.71% and 94 ± 2.71%. According to <em>in vitro</em> investigations, liposomes as a delivery system for the nasal route provided a more sustained drug release than the oral dosing form.</p></div><div><h3>Conclusions</h3><p>The intranasal administration of venlafaxine liposomal vesicles effectively enhanced the absolute bioavailability, retention time, and brain delivery of venlafaxine.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"99 ","pages":"Article 100714"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b4/f9/main.PMC10506098.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}